tbuckley/cabot-search huggingface dataset:
Cost-effectiveness analysis (CEA) of seven treatment regimens in metastatic hormone-sensitive prostate cancer (mHSPC): A public payer perspective using network meta-analysis.
Authors: Manish Kohli, Maura Dougherty, Zachary Cutshall, Rylee Beckstead, Rhea Kohli, Benjamin Haaland, Richard Nelson, Minkyoung Yoo
Journal: Journal of Clinical Oncology (2023)

5081 Background: Recently several new drug treatment regimens have been approved in mHSPC state, building on using androgen deprivation therapy (ADT) alone. These include docetaxel + ADT (DA), Abiraterone Acetate + Prednisone + ADT (AAP), Apalutamide + ADT (AAT), Enzalutamide + ADT (ET), Darolutamide + Docetaxel + ADT (DAD) and AAP + ADT + Docetaxel (AAD). At present, there are no predictive biomarkers for choosing a specific drug regimen over the other. The goal of this study was to conduct an economic evaluation of FDA-approved standard of care drug regimens in the current management of mHSPC state to determine a cost-effective optimal treatment from the US public sector (Veterans Affairs-VA) perspective with a 10-year time horizon. Methods: We developed a partitioned survival model in which mHSPC patients (pts) transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a network meta-analysis. A Bayesian network meta-analysis of seven randomized clinical trials included 7,208 mHSPC pts. The effectiveness outcome in our model was quality-adjusted life-years (QALYs) with utility values obtained from published literature. Costs in our model included those associated with treatment regimens, subsequent therapies, terminal care, and for managing grade 3-4 drug related adverse events. Costs were obtained from the Federal Supply Schedule and published literature. Incremental cost-effectiveness ratios (ICERs) were calculated for nondominated treatments. Results: Average 10-year costs ranged from $32,697 (ADT) to $649,622 (DAD). Mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment with DAT, EAD, and DAD were eliminated due to dominance (i.e. they were more costly and less effective than other treatments). AAT was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $70,150/QALY). Results from our analysis for all regimens are shown. Conclusions: Our CEA simulation model found AAT is an optimal cost-effective first-line treatment strategy in mHSPC state from a public (VA) payer perspective. [Table: see text]
EGFR/ERBB2 aberrations in Chinese biliary tract carcinomas.
Authors: Xiaobing Wu, Yaping Zhao, Chenxi Wang, Ran Ding, Wanglong Deng, Fanfeng Bu
Journal: Journal of Clinical Oncology (2023)

e16208 Background: Biliary tract carcinoma (BTC) accounts for 3% gastrointestinal cancers in China. BTCs are mainly classified as gallbladder cancer (GBC) and cholangiocarcinomas (CCA) with dismal prognosis. Current chemotherapy regimens for BTC yield poor outcomes. We aimed to describe the genomic landscape of a BTC patient cohort using next-generation sequencing (NGS), focusing on the EGFR/ERBB2 aberrations and exploring the possibility of therapeutic intervention. Methods: We analyzed BTC tissue/blood samples including GBCs and CCAs with targeted sequencing (NGS) for EGFR/ERBB2 activating mutations, copy number amplifications (copy number≥5) and rearrangements (containing the kinase domain). A cohort of 1033 Chinese BTC patients were analyzed including 783 GBC patients and 250 CCA patients. Results: Data analysis revealed EGFR/ERBB2 alteration rates were 9.0% in Chinese BTC patients. The majority of these alterations were in fact ERBB2 alterations at a rate of 15.8% in GBC and 6.4% in CCA（P&lt;0.05). A further subanalysis of ERBB2 mutation types showed that 46.7% in GBC and 64.6% in CCA were activating mutations, 37.8% in GBC and 31.3% in CCA were gene amplifications, 8.9% in GBC and 2.1% in CCA were gene rearrangements and 6.7% of GBC and 2.1% of CCA cases had multiple ERBB2 alterations. The top activating ERBB2 mutation were p.S310F（10/45） followed by p.R678Q(4/45) in GBC and were p.S310F (11/48) followed by p.V777L(5/48) in CCA. EGFR alteration rates were 3.5% in GBC and 1.3% in CCA（P&lt;0.05). Among these, 30% of the GBCs and 60% of the CCAs had an activating EGFR mutation, 70% of the GBCs and 30% of the CCAs had EGFR copy number amplification and 10% of the GBCs and no CCA case had an EGFR rearrangement. Three EGFR activating mutations detected in GBC were p.G719A, p.L861Q, p.A289V. Six EGFR activating mutations detected in CCA were p.G719D, p.E746_S752delinsV, p.L858R, p.N771_H773dup, p.D770_N771insG, p.R222C. Conclusions: We report characteristics of EGFR/ERBB2 alterations in Chinese GBC and CCA patients. In general, 19.4% of GBC and 7.7% CCA may benefit from EGFR/ERBB2 targeted therapy. EGFR/ERBB2 targeted therapies should be further explored in Chinese BTC patients.
Relationship of platelet-to-lymphocyte ratio with tumor immune microenvironment and efficacy of anti-PD-1 combined with neoadjuvant chemotherapy in muscle invasive bladder cancer.
Authors: Hailong Hu, Yuanjie Niu, Hong Zheng Li, Zesheng An, Zhouliang Wu, Chong Shen, Zhe Zhang, Gangjian Zhao, Shiwang Huang
Journal: Journal of Clinical Oncology (2023)

e14549 Background: The platelet-to-lymphocyte ratio (PLR) has been used to predict therapeutic response in different tumors. However, no assessments of its usefulness have been performed in muscle-invasive bladder cancer (MIBC) patients receiving anti-PD-1 combined with neoadjuvant chemotherapy. Methods: The respective data of 62 MIBC patients receiving anti-PD-1 combined with neoadjuvant chemotherapy were analyzed. Whether PLR might predict treatment response to anti-PD-1 plus neoadjuvant chemotherapy and the cutoff value of the parameter were determined by ROC curve analysis. Moreover, 31 tumor mRNA sequencing data before the treatment were collected and analyzed using ESTIMATE R package. Results: PLR before the second period (PLR2, cut-off = 122.38, AUC = 0.667, 95% CI: 0.529-0.805, sensitivity = 0.935, specificity = 0.452) seemed to be useful predictors to determine patients who have a response or no response. The PLR2-low and PLR2-high groups were divided according to median score (154.9), and the estimate score and the immune score were significantly higher in the PLR2-low group. Conclusions: The PLR2 allowed for the accurate and efficient stratification of MIBC patients receiving anti-PD-1 plus chemotherapy and is easily applicable for clinical practice at no additional cost. Meanwhile, we identified that the diagnostic performance of PLR2 might reflect the tumor immune microenvironment, which plays an important role in immune therapy.
A quantitative synthesis of disparities in the inclusion of racial/ethnic minorities and older women in breast cancer trials.
Authors: Mahnoor Islam, Syed Arsalan Ahmed Naqvi, Muhammad Daim Bin Zafar, Ahsan Ayaz, Yusra Saleem, Atiqa Khalid, Muhammad Hisham Khan Wazir, Hafsah Ijaz, Karthik Giridhar, Siddhartha Yadav, Brenda Ernst, Irbaz Bin Riaz
Journal: Journal of Clinical Oncology (2023)

6557 Background: Trials that inadequately include underrepresented minority (URM) populations widen inequities in cancer care. We assessed reporting patterns, representation, and trends of URM representation in breast cancer (BC) trials. Methods: We analyzed all phase 2/3 trials for age disparity and trials recruiting from the US for racial/ethnic disparity amongst BC RCTs (1990-2021). Enrollment-incidence ratios (EIR), which compare trial proportions (TP) from age subgroups against global estimates of incidence in the corresponding age group (from Global Burden of Disease) and racial/ethnic subgroups against US-population-based incidence in the corresponding racial/ethnic group (from SEER 22), were calculated. Individual-trial EIRs were pooled using random-effects meta-analyses. EIRs of &lt;0.80 indicated meaningful underrepresentation, while EIRs &gt;1.20 indicated meaningful overrepresentation. Meta-regression was used to explore associations between key trial characteristics and EIR, and trends in EIR over the last three decades. Results: Of 842 global trials with 490,657 participants, 232 (27.6%) reported the number of participants in specific age strata and 144 (17.1%) reported outcomes by age. Only 60 trials recruited exclusively from the US. Of these, 41 (68.3%) reported race and 24 (40.0%) reported ethnicity, and 2 (3.3%) analyzed outcomes by race. Older adults aged ≥65 years (TP: 24.3%; EIR: 0.53 [95% CI: 0.47-0.60]) and Hispanic women (TP: 5.3%; 0.54; 0.40-0.75) were underrepresented across global trials and US-only trials respectively. Black women were significantly underrepresented in trials that led to FDA approval (0.38; 0.25-0.58) but not in US-only trials. Stratified analysis by BC subtype (with subtype-specific population incidence) showed underrepresentation of Black women in US-only trials for HER2+ BC (0.66; 0.47-0.93), Hispanic women in ER+ BC (0.42; 0.20-0.90), Asians in triple-negative BC (0.24; 0.11-0.53), and older women in HER2+ BC (0.35; 0.31-0.40) and triple-negative BC (0.36; 0.29-0.45). From 1990-2021, the representation of older women declined significantly (meta-regression coefficient for EIR: -0.4 per 10 years), while Black and Hispanic representation showed no significant change. Black (p = 0.02) and Hispanic representation (p = 0.05) worsened significantly in larger trials. Conclusions: Published reports of BC trials do not consistently report the inclusion of URM. Older and Hispanic women were consistently underrepresented, whereas Black women were underrepresented in large, practice-changing trials. [Table: see text]
The value of progression-free survival at three years as a primary endpoint for studies on radiotherapy in patients with locally advanced cervical cancer: Individual patient data from Chinese National Cancer Center and validation from 27 global randomized trials.
Authors: Xi Yang, Jusheng An, Yuanyuan Zhang, Yong Yang, Shuangzheng Jia, Wei Li, Manni Huang, Lingying Wu
Journal: Journal of Clinical Oncology (2023)

5534 Background: A traditional endpoint for locally advanced cervical cancer (LACC) clinical trials is overall survival with five years of follow-up (5-year OS). The use of a shorter-term endpoint could significantly speed the translation of research findings into practice. The primary hypothesis was that PFS with three years of follow-up (PFS36) is an appropriate primary endpoint to replace 5-year OS. Methods: The primary hypothesis was developed from our individual data, was further investigated using phase III randomized controlled trials (RCTs), and then externally validated by phase II trials and retrospective studies up to 2022. Correlation analysis at the treatment-arm level was performed between 2-, 3-, 4-, and 5-year PFS rates and 5-year OS. Correlation analysis was performed using the Pearson correlation coefficient r in weighted linear regression, with weight equal to patient size. The MEDLINE, Embase, and PubMed databases, together with the Cochrane Central Register of Controlled Trials, were searched from January 1, 1999, to February 2, 2023. Articles eligible for inclusion contained complete survival data. Results: A total of 613 patients with histologically confirmed, FIGO 2009 stage IB–IVA cervical cancer who underwent radiotherapy at our institute from January 2010 to December 2013 were eligible. Individual patient data were pooled to explore the correlation between PFS and the OS trend. The recurrence rates for years 1 through 5 were 12.9%, 7.3%, 3%, 2.3%, and 1.8%, respectively. The median recurrence time was 13 months and the median time from recurrence to death was 12.2 months. Within all the recurrence, 47.3% of recurrences occurred during the first year, 71.4% in the first two years, and 85% in the first three years. Patients who did not achieve PFS36 had a 5-year OS rate of 30.3%. In contrast, a 5-year OS rate of 98.2% was observed in patients who achieved PFS36. Further data were extracted from 27 randomized phase III trials on LACC. The trials included 57 arms, with a pooled sample size of 7,692 patients. In trial-level surrogacy, PFS36 (r 2 , 0.778) was associated with 5-year OS. Sensitivity analysis demonstrated reasonable overall consistency. The correlation between PFS36 and OS was externally validated using independent phase II trials and retrospective data. In total, 23 studies representing 5,174 patients were included. PFS (r 2 , 0.719) was found to be associated with 5-year OS. Conclusions: A significant correlation was found between PFS36 and 5-year OS in clinical trials on patients with locally advanced cervical cancer. This correlation was found both within patients and across trials. These results suggest that PFS36 is an appropriate endpoint for LACC trials of radiotherapy-based regimens.
C-reactive protein (CRP) as a prognostic biomarker in patients with bladder cancer: A meta-analysis.
Authors: Yu Fujiwara, Alexander B. Karol, Emma Reford, Himanshu Joshi, Deborah Blythe Doroshow, Matt D. Galsky
Journal: Journal of Clinical Oncology (2023)

e16502 Background: CRP is an acute phase reactant synthesized by hepatocytes in response to inflammatory cytokines including interleukin-6. Peripheral blood CRP, a routinely measured analyte, may reflect tumor microenvironments skewed towards tumor-promoting inflammation. CRP may therefore represent an attractive biomarker to select patients with bladder cancer (BCa) more likely to benefit from therapies directed at modulating tumor-promoting inflammation. Methods: A systematic review was performed to identify studies reporting outcomes based on pre-treatment CRP values in patients with localized and advanced BCa and urothelial carcinoma (UC). The hazard ratio (HR) of overall survival (OS), cancer-specific survival (CSS), relapse-free survival (RFS), and progression-free survival (PFS) between groups with high and low CRP values as defined in each study was extracted. Meta-analysis using the random-effect model was performed to pool HR. Meta-regression analysis was conducted to assess the relationship between CRP cutoff and HR for OS. Subgroup analyses were performed according to clinical disease state and therapies administered. Heterogeneity was assessed using I 2 statistics. Results: Overall, 938 articles were identified at initial screening; 22 studies comprising 2,899 patients were included in the meta-analysis. For OS, 17 datasets from 16 studies were used. High CRP levels were associated with decreased OS (HR=2.03, 95%CI:1.67-2.47, p&lt;0.01) although high heterogeneity was observed (I 2 =91%). Subgroup analyses according to anticancer interventions showed that high CRP values were related to shorter OS, particularly in patients treated with immune checkpoint blockade (ICB; HR=1.78, 95%CI: 1.47-2.15, p&lt;0.01). In meta-regression analysis, the correlation between CRP cutoff value and OS HR was not observed when all 16 studies were considered (Regression coefficient=0.03, 95%CI: -0.13-0.18, p=0.73). However, CRP cutoff value was significantly associated with the HR for OS (Regression coefficient=-0.21, 95%CI: -0.36 to -0.06, p=0.01) when the analysis was limited to eight studies assessing ICB in advanced BCa/UC. Pooled HR of CSS, RFS, and PFS is shown in Table. Conclusions: High CRP values were associated with poorer clinical outcomes in patients with BCa/UC, particularly among patients with advanced disease treated with ICB. CRP may represent an attractive biomarker to enrich populations more likely to benefit from therapies that modulate tumor-promoting inflammation. [Table: see text]
Consensus molecular subtypes and orphan non-coding RNAs in colorectal cancer.
Authors: Jeffrey Wang, Mehran Karimzadeh, Taylor B. Cavazos, Afsaneh Barzi, Kathleen Wang, Rose Hanna, Patrick Arensdorf, Kimberly H. Chau, Helen Li, Hani Goodarzi, Lisa Fish, Fereydoun Hormozdiari, Babak Alipanahi
Journal: Journal of Clinical Oncology (2023)

e15651 Background: Colorectal cancer (CRC) is a highly heterogeneous disease with variable response to different treatment strategies. The consensus molecular subtype (CMS) classification system has been proposed as a gene expression-based framework aimed at capturing the genetic and molecular heterogeneity in CRCs and potentially stratifying patients into clinically relevant subgroups for treatment selection. We previously demonstrated that orphan non-coding RNAs (oncRNAs), a novel class of cancer enriched small non-coding RNAs (smRNA), exhibit cancer-specific expression. We also showed that oncRNAs can be used in a liquid biopsy assay for accurate early-stage detection of CRCs. We hypothesize that oncRNAs may be informative of CRC subtype-specific transcriptional signatures as defined by the CMS groups. Methods: To assess the effectiveness of oncRNAs for categorization of CMS group, we examined smRNA-seq data from The Cancer Genome Atlas (TCGA) for colon and rectal adenocarcinoma tumors ( n= 504), consisting of 77 CMS1, 216 CMS2, 71 CMS3, and 140 CMS4 tumors. CRC-specific oncRNA expression profiles were generated for all tumors in the TCGA cohort. We then trained a machine learning model on oncRNA expression profiles to predict CMS groups using a 5-fold cross validation setup. For our validation cohort, we applied our model to an independent CRC cohort ( n= 348) consisting of 56 CMS1, 101 CMS2, 59 CMS3, and 132 CMS4 CRC samples. Final CMS predictions for the validation cohort were made by averaging across the five training models. Results: Within TCGA testing folds, the model micro-averaged ROC-AUC for CMS classifications were 0.879 (95% CI: 0.86–0.90). In the validation cohort, micro-averaged AUC remained high at 0.915 (0.90–0.93). Sensitivities and AUCs for each subtype are provided in Table 1. The highest model-predicted likelihood for each CMS subtype had an accuracy of 73.6% (68.6%–78.1%), and the two most probable predictions had an accuracy of 91.1% (87.6%–93.9%). Conclusions: This study demonstrates the utility of oncRNA expression profiling to predict CMS for colorectal cancer. The generalizability of our machine learning model suggests that oncRNAs are informative of the biological differences across distinct CMS groups and may be used as a proxy for gene expression signatures to stratify colorectal cancers. Because smRNAs are more likely to be secreted into blood, we posit that an oncRNA-based liquid biopsy may open new opportunities to monitor patients and track changes in their tumor biology in real-time throughout their course of disease and treatment. [Table: see text]
Huaier granules for hepatocellular carcinoma recurrence after ablation: A multicenter prospective cohort study.
Authors: Yue Han, Jiasheng Zheng, Chidan Wan, Zixiang Li, Bo Zhai, Jiaping Li, Yuliang Li, Hailiang Li, Liwei Ma, Ruibao Liu, Jun Zhou, Lei Shi, Lei Song, Shuai Wang, Juqiang Han, Bo Zhang, Qingdong Li, Xin Ye, Weijun Fan
Journal: Journal of Clinical Oncology (2023)

e16216 Background: Clinical trials had confirmed the efficacy and safety of Huaier granules in the treatment of hepatocellular carcinoma (HCC), but real-world evidence is still lacking. This prospective study aimed to evaluate the real-world effectiveness and safety of Huaier granules for HCC recurrence after ablation. Methods: Post-ablation patients with no residual lesions confirmed by imaging were enrolled in this study and divided into the Huaier granule group and the control group based on receiving Huaier granules or not. Propensity-score matching was performed according to age, gender, TACE within 3 months before ablation, alpha-fetoprotein level, time interval between ablation and enrollment, and Child-Pugh Grade in 1-(up)-to-2 ratio. The primary outcome was progression-free survival (PFS), and the secondary outcomes were local recurrence-free survival (LRFS) and adverse events (AEs). Results: There were 340 patients in the Huaier granule group and 141 patients in the control group. After propensity score matching, 189 patients and 111 patients were selected for the Huaier granule group and the control group, respectively. There was no significant difference in baseline characteristics between two groups after matching. The median follow-up time of the Huaier granule group and the control group were 49.14 weeks and 73.29 weeks, respectively. The number of PFS events were 29 (15.34%) and 27 (24.32%) in the Huaier granule group and the control group, respectively. The 48, 72, and 96-week PFS rates were 87.4%, 79.4% and 75.2% in the Huaier granule group, and 79.9%, 70.1% and 66.5% in the control group, respectively ( P=0.1649). The number of LRFS events were 27 and 25 in the Huaier granule group and the control group, respectively. In the pre-matching Huaier granule cohort, the incidence of AEs, serious AEs, and grade ≥ 3 AEs were 54 (16.56%), 30 (9.20%) and 14 (4.30%), respectively. Conclusions: This study suggested potential benefit in PFS and RFS and favorable safety profile of Huaier granules in patients with HCC after ablation. Longer-term follow-up is needed to confirm this finding.[Table: see text]
Risk of early mortality in patients with cancer experiencing adverse financial events.
Authors: Hiba Khan, Li Li, Kaiyue Yu, Catherine R. Fedorenko, Karma L. Kreizenbeck, Sara Khor, Shannon Kestner, Scott David Ramsey, Veena Shankaran
Journal: Journal of Clinical Oncology (2023)

6503 Background: Patients with cancer are at higher risk for experiencing severe adverse financial events (AFEs) compared to similar individuals without cancer. Among persons with cancer, those experiencing bankruptcy have poorer survival. In this study, we sought to determine whether AFEs less severe than bankruptcy have an increased risk of death among patients with cancer. Methods: Records for all patients diagnosed with a solid tumor between 2013 and 2018 were identified through the Western Washington State SEER cancer registry and were linked to quarterly credit reports from TransUnion. Patients who survived at least 2 years from date of diagnosis were included. Cancer patients experiencing any AFE, defined as third-party collections, charge-offs, delinquent mortgage payments, tax liens, foreclosures, and repossessions within 2 years of diagnosis were compared with cancer cases who did not experience these events. After adjusting for age, sex, race, area deprivation index, rural/urban status, marital status, AFE at diagnosis, cancer type, and stage of cancer, we fit a Cox proportional hazards model to examine the relationship between AFEs and overall survival, and also fit a separate model for each cancer type. Results: A total of 64,637 patients were diagnosed with cancer between 2013 and 2018, and survived 2 years post-diagnosis. The overall population was 84% white, 53% female, and had a median age of 64. 12,698 patients experienced any severe financial event. The adjusted hazard ratio for mortality among patients who did versus did not experience an AFE was 1.22 (95% CI, 1.145-1.299, p &lt;0.001), with age &gt;65, Asian/Pacific Islander race, greater area deprivation index, and higher stage of cancer associated with increased risk for mortality. Among differing cancer types, patients with prostate cancer who experienced an AFE had the highest risk of death compared with patients with prostate cancer who did not experience an AFE (HR 1.703,95% CI, 1.395 to 2.08, p &lt;0.001). Conclusions: Patients with cancer who experience severe AFEs within 2 years of diagnosis are at higher risk for mortality after adjusting for sociodemographic and clinical factors. When comparing within separate cancer groups, this association is strongest among patients with prostate cancer. Current analysis is limited by restricting population to those who survived at least 2 years after diagnosis; future work will expand population to include patients who died at any time point. Further research should investigate mechanisms for this increased mortality risk, to inform potential interventions and policy solutions, especially among the prostate cancer population. [Table: see text]